The aim of the present research plan is to study the metabolism and regional blood flow in the brain in situations that lead to hypoxic tissue damage, and to define the mechanisms that cause such damage. The ultimate objective of the research is to help define therapeutic measures that may improve restitution of cerebral function in reversible forms of cerebral hypoxia, and prevent the development of irreversible damage. In order to achieve these aims clinically prevalent forms of cerebral hypoxia, especially those caused by regional or global ischemia will be reproduced in animal experiments. The metabolism of the tissue will be evaluated from blood flow and arteriovenous differences of substrates and products of metabolism, as well as from the tissue contents of organic phosphates, glycolytic substrates, citric acid cycle intermediates and amino acids. Cerebral blood flow will be measured both globally, using methods that allow quantification of metabolic rates, and regionally. Correlations will be sought to changes in cerebral metabolism of neurotransmitters, in neurophysiological patterns of activity, and in brain histology. A special interest will be devoted to measures that improve circulation in hypoxic tissue areas, or protect the tissue against harmful effects of oxygen deprivation.